Biomedical Engineering Reference
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Fig. 2 Bounded convex hull
in the space of yields of
biomass (blue crosses) and
product (green crosses)on
glycerol and oxygen
phosphate (NADPH
2
), flavin adenine dinucleotide (FADH
2
), and H
2
O were also
accounted for in the metabolic reactions in order to close the balance of oxygen,
hydrogen, and phosphorus. It was assumed a fixed P/O ratio of 2 mol-ATP/mol-
NAD(P)H
2
and of 1 mol-ATP/mol-FADH
2
. The resulting metabolic network for
glycerol as carbon source has 104 reactions (thus 104 fluxes), 90 intracellular
metabolites, and 16 extracellular metabolites (17 % of all metabolites).
The open-source bioinformatics software METATOOL 5.0 [
31
] was used to
compute the elementary modes of the P. pastoris metabolic network. The total
number of elementary modes was 4,119. Figure
2
shows a representation of the
yields of biomass and product on glycerol and oxygen obtained through stoichi-
ometric analysis of elementary modes.
The number of elementary modes for glycerol feeding was 2,520, 960, 600, and
39 for biomass growth, scFv synthesis, simultaneous biomass growth and scFv
synthesis, and catabolism, respectively. From Fig.
2
it can be seen that the yields on
glycerol for biomass growth and scFv synthesis vary from 0.42 to 0.73 g-X/g-S and
0.26 to 0.64 g-X/g-S, respectively, and that the yields on oxygen increase with the
yields on glycerol. The elementary modes with lowest yields on glycerol and oxygen
are those that include the metabolic reactions involved in the secretion of organic
acids from TCA, namely succinate for biomass growth and citrate for scFv synthesis.
On the other hand, the elementary modes with the highest yields on glycerol and
oxygen involve the metabolic reaction of the pentose phosphate pathway.
3 Measuring the Envirome
The whole set of physical and chemical properties that define the environment of
cells is known as the ''envirome''. The envirome is the critical layer of information
for bioprocess monitoring and control, since it can be readily measured and/or
manipulated in real time. The vast majority of envirome components are also
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